Heart failure (HF) is a major public health concern, affecting more than 5.5 million Americans, with over 550,000 new cases diagnosed each year, and accounting for up to 10% of all hospital admissions. Depression is the most robust behavioral predictor of morbidity and premature mortality among patients with symptomatic HF, with an incidence ranging from 20% to 45%, depending on HF severity. Our ongoing project HL-073355 is examining the pathophysiology associated with depression in HF patients. Few studies have systematically examined the development and progression of depression concurrent with the development of and progression to symptomatic HF and its associated neuroimmune and behavioral mechanisms. By enrolling individuals at risk for developing symptomatic HF but who are currently asymptomatic, namely American College of Cardiology/American Heart Association (ACC/AHA) Stage B patients, this competing renewal of HL-073355 will prospectively track the incidence and time course of depressive symptoms and Major Depressive Disorder (MDD), the development of symptomatic HF, potential neuroimmune and behavioral mechanisms linking HF and MDD, and associations with cardiovascular clinical outcomes. We will enroll 522 high-risk (defined as BNP >100pg/ml) ACC/AHA Stage B patients, study them at intake, and every 6 months for an average of 30 months. Through our strong collaborations with the HF teams at the University of California, San Diego (UCSD) Hillcrest and La Jolla Medical Centers, and the Veterans Affairs San Diego Healthcare System (VASDHS) in La Jolla, we have access to a large number of asymptomatic Stage B patients. Clinical assessments will include echocardiography and characterization of depressive symptoms by the Beck Depression Inventory (BDI) and the Structured Clinical Interview for DSM Disorders (SCID). Neuroimmune assessments will include circulating levels of BNP, CRP, TNF-1, IL-12, IL-6, sICAM-1, sP-selectin, catecholamines, and functional assessments of leukocytes. In addition to depression, other behavioral and psychosocial assessments will include sleep, health behaviors (e.g., smoking, physical activity), psychosocial stressors, coping, anxiety, social network, and quality of life. Clinical outcomes will include transition from asymptomatic cardiac dysfunction to symptomatic Stages C and/or D HF, clinical cardiovascular outcomes (combined hospitalizations for cardiovascular events and/or death), and the development or recurrence of MDD. Findings from this prospective study have the potential to add new insights into how MDD might contribute to HF progression at early stages of the disease. A greater understanding of the role and mechanisms by which MDD may impact HF at this stage could support clinically relevant early MDD intervention efforts at a point when effective depression treatment could have a potentially greater impact on the course of HF. PUBLIC HEALTH RELEVANCE: Depression is the most robust behavioral predictor of morbidity and premature mortality among patients with heart failure, although the mechanisms of this relationship are poorly understood. In a cohort of American College of Cardiology/American Heart Association (ACC/AHA) classification asymptomatic Stage B patients, we will prospectively track depressive symptoms, the development and progression to symptomatic Stages C/D heart failure, and associations with adverse clinical cardiovascular outcomes, as well as determine potential neuroimmune and behavioral and psychosocial mechanisms within a naturalistic framework.